Regulation of cell proliferation by insulin-like growth factor 1 in hyperoxia-exposed neonatal rat lung

Molecular Genetics and Metabolism
A Chetty, H C Nielsen

Abstract

Hyperoxic exposure of the developing lung leads to characteristic peribronchial and mesenchymal fibroproliferative changes. We hypothesize that O2-induced changes in the neonatal lung are mediated by Insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R). Lung explant cultures were prepared from 3-day-old neonatal rat pups and exposed to room air or 95% O2 for 72 h. Western blots and immunohistochemistry were used to determine if hyperoxia stimulated IGF-1 and IGF-1R, and to identify the cell types involved. Retinoic acid was used to learn if this would inhibit oxygen-induced cell proliferation. Hyperoxia induced a significant increase in thymidine incorporation (control, 54 +/- 9; hyperoxia, 254 +/- 24 dpm/nM DNA; mean +/- SEM; N = 3; P < 0.05). This was inhibited by 5 x 10(-5) M RA (149 +/- 18 dpm/nM DNA; P < 0.05) and by anti-IGF-1 antibody (115 +/- 25 dpm/nM DNA; P < 0.05; N = 3). BrdU labeling in the mesenchymal cells was significantly increased in mesenchymal cells after exposure to oxygen (91% higher than the room air control) but not in epithelial cells. This increase was inhibited in the presence of retinoic acid. Western blots showed IGF-1 protein was increased after 72 h of O2 exposure compared to room air ...Continue Reading

Citations

Jun 18, 2009·Critical Care Medicine·Shyoko Honiden, Michelle N Gong
Apr 12, 2012·American Journal of Respiratory Cell and Molecular Biology·Tae-Hyung KimLynn M Schnapp
Oct 10, 2013·Respiratory Research·Chi F HungLynn M Schnapp
Apr 12, 2005·Respiratory Research·Karmene AhamedAlexandra Henrion-Caude
Apr 9, 2005·Pediatric Research·Jacques BourbonChristophe Delacourt
Jul 27, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jawed NawabiMiguel A Alejandre Alcazar
Aug 2, 2005·Pediatric Research·Anne ChettyHeber C Nielsen
Jun 5, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Katja ZscheppangChristiane E L Dammann
Dec 12, 2018·Molecular Medicine Reports·Jing HeChuanwang Song
Mar 5, 2013·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jun LiA Keith Tanswell
Jul 19, 2018·BioMed Research International·Zheng WangXiaoju Zhang
Dec 18, 2004·Journal of Cellular Physiology·Ekaterina ShumilinaFlorian Lang

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